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  • Phasic contractions are driven by slow waves generated by pacemaker ICC – depolarizations enable Ca2+ Entry – action potential – electromechanical Coupling Motility of GI tract is results from coordinated contractions of smooth muscle, which in turn derive from two basic patterns of electrical activity across the membranes of smooth muscle cells — slow waves and action potentials.[2] Slow waves are initiated by pacemakers — the interstitial cells of Cajal (ICC). Slow wave frequency varies in the different organs of the GI tract and is characteristic for that organ. They set the maximum frequency at which the muscle can contract: stomach — about 3 waves in a minute – during fasting, these do not result in contractions. For 2-3 hours after meals, spikes are superimposed on slow waves – result in contractions that propogate distally. Bradygastria – assocaited with GP Tachygastria Disorganised – dysrthythmia duodenum — about 12 waves in a minute, ileum — about 8 waves in a minute, rectum — about 17 waves in a minute.[3] jejunum — about 11 waves in a minute.[4]
  • The diabetic patient with nausea and vomitingas predominant symptoms is the best candidate for GES.
  • Gastroparesis

    1. 1. Abeezar I. Sarela Consultant in Upper GI & Bariatric Surgery Hinduja Hospital, Mumbai St James’s University Hospital, Leeds, UK Gastric Motility Disorders
    2. 2. Case Study <ul><li>52 year old woman </li></ul><ul><li>Fullness after a small meal </li></ul><ul><li>Continuous nausea </li></ul><ul><li>6-8 episodes of vomiting daily </li></ul><ul><li>Upper abdominal bloating </li></ul><ul><li>Diabetes </li></ul><ul><ul><li>Insulin, Metformin, Exenatide </li></ul></ul>
    3. 3. Endoscopy Barium Meal and Follow-Through CT scan
    4. 4. Functional Dyspepsia?
    5. 5. Gastroparesis <ul><li>Delayed gastric emptying in the absence of mechanical obstruction of the stomach </li></ul>
    6. 6. True Prevalence? <ul><ul><li>25-40% </li></ul></ul><ul><ul><li>of “dyspeptic” patients </li></ul></ul>American Gastroenterological Association Technical Review on the Diagnosis and Treatment of Gastroparesis. Gastroenterology 2004;127:1592-1622
    7. 7. Aetiology of Gastroparesis <ul><li>Idiopathic </li></ul><ul><li>Diabetes mellitus </li></ul><ul><li>Post-surgical </li></ul><ul><ul><li>Partial gastric resection/vagotomy </li></ul></ul><ul><ul><li>Bariatric surgery </li></ul></ul><ul><ul><li>Anti-reflux surgery </li></ul></ul><ul><li>Associated with other GI disorders </li></ul><ul><li>Associated with Non-GI disorders </li></ul>American Gastroenterological Association Technical Review on the Diagnosis and Treatment of Gastroparesis. Gastroenterology 2004;127:1592-1622
    8. 8. Diabetic Gastroparesis <ul><li>5-12% of diabetics </li></ul><ul><ul><li>Long duration of disease ~ 10 years </li></ul></ul><ul><ul><li>Neuropathy, nephropathy, retinopathy </li></ul></ul>
    9. 9. Diabetic Gastroparesis <ul><li>Destabilisation of blood glucose control </li></ul><ul><ul><li>Alteration in drug absorption </li></ul></ul><ul><ul><li>Unpredictable delivery of food into intestine </li></ul></ul><ul><li>Hyperglycemia affects gastric motility </li></ul><ul><li>Problems with blood glucose control may be first indication of gastroparesis </li></ul>
    10. 10. Diagnosis Nuclear Medicine Gastric Scintigraphy
    11. 11. Normal Liquid Emptying from Stomach Exponential Curve ~ Measure T½
    12. 12. Normal Emptying of Solid Food from Stomach
    13. 13. Normal Emptying of Solid Food from Stomach Linear Pattern ~ Measure Proportion Retained in Stomach At 1 hours and 4 hours
    14. 14. Measuring Gastric Emptying Dual Phase Scintigraphy <ul><li>Scintigraphy uses different radionuclides for labeling the liquid and solid elements of the meal so that emptying curves for both phases are obtained simultaneously </li></ul>
    15. 15. Normal Gastric Emptying
    16. 16. N ormal Pattern <ul><li>Liquid phase </li></ul><ul><ul><li>T½ less < 30 minutes </li></ul></ul><ul><li>Solid phase </li></ul><ul><ul><li>at least 25% of the meal leaves the stomach by 60 minutes </li></ul></ul><ul><ul><li><15% is retained in the stomach at 4 hours </li></ul></ul>
    17. 17. Gastroparesis solid liquid
    18. 18. liquid solid Gastroparesis
    19. 19. Gastric Emptying N Eng J Med 2007; 356:820-829
    20. 20. Other Tests <ul><li>13 C Labelled Octanoate Breath Test </li></ul><ul><li>Antroduodenal Manometry </li></ul><ul><li>Electrogastrography </li></ul><ul><li>Ultrasound </li></ul><ul><li>Magnetic Resonance Imaging </li></ul>
    21. 21. Why is Scintigraphy the Investigation of Choice? <ul><li>Simple </li></ul><ul><li>Non-invasive </li></ul><ul><li>Very small radio-active dose </li></ul><ul><li>Physiological </li></ul><ul><li>Prolonged observation </li></ul><ul><li>Quantifiable </li></ul>
    22. 22. Severity of Gastroparesis N Eng J Med 2007;356:820-829 Yes No No Non-pharmacologic treatment Jejunal tube By mouth Rare Nutritional supplements Routine Sometime Rare Homogenised food >35% 16-35% 10-15% Retention at 4 hours Severe Moderate Mild
    23. 23. Treatment of Gastroparesis
    24. 24. 1. Correction of Exacerbating Factors
    25. 25. 2. Nutrition Homogenised Diet Jejunal Tube Feeding
    26. 26. 3. Symptomatic Treatment <ul><li>Macrolides </li></ul><ul><ul><li>Erythromycin </li></ul></ul><ul><li>Dopamine Receptor Antagonists </li></ul><ul><ul><li>Metoclorpromide </li></ul></ul><ul><ul><li>Erythromycin </li></ul></ul><ul><li>Anti-emetics </li></ul><ul><li>Analgesia </li></ul>
    27. 27. 3. Symptomatic Treatment <ul><li>Botox injection at pylorus </li></ul><ul><li>Surgery </li></ul><ul><li>Gastric Electrical Stimulation </li></ul>
    28. 28. Gastric Smooth Muscle Function <ul><li>Gastric slow waves (Phasic): 3/min </li></ul><ul><ul><li>Bradygastria, Tachygastria, Gastric Dysrhythmia </li></ul></ul><ul><li>Tonic spikes superimposed on slow waves result in smooth muscle contraction </li></ul>Soffer et al. Aliment Pharmacol Ther 2009;30:681-694
    29. 29. Gastric Electrical Stimulation (GES) <ul><li>Gastric Pacing: </li></ul><ul><li>Entrain slow waves </li></ul><ul><li>Low-frequency + Long duration </li></ul><ul><li>Implantable Pulse Generator (IPG) not available </li></ul><ul><li>Implantable GES </li></ul><ul><li>High frequency + Short duration </li></ul><ul><li>Slow waves not altered </li></ul><ul><li>Neural stimulation </li></ul>Clinically Used GES is NOT pacing
    30. 30. Enterra ™ Therapy (Medtronics) for Gastroparesis <ul><li>Humanitarian Device Exemption approval from the US FDA in 2000 </li></ul><ul><li>Handheld, external programmer to adjust the neurostimulator and customize therapy </li></ul><ul><li>Therapy can be turned off at any time </li></ul>
    31. 31. Electrophysiology of Enterra ™ Therapy <ul><li>High-Frequency stimulation with </li></ul><ul><li>trains of </li></ul><ul><li>Short-Duration pulses </li></ul>Soffer et al. Aliment Pharmacol Ther 2009;30:681-694
    32. 32. Enterra ™: Position of Electrodes 9 cm 10 cm 1 cm
    33. 33. Implantation of Enterra ™ Electrodes
    34. 34. Enterra ™ Therapy <ul><li>~ 1000 devices used world-wide </li></ul><ul><li>Largest experience: </li></ul><ul><ul><li>University of Mississippi Medical Centre, Jackson, USA </li></ul></ul><ul><ul><li>~ 600 cases </li></ul></ul><ul><li>UK </li></ul><ul><ul><li>8 regional centres </li></ul></ul>
    35. 35. <ul><li>Improvement in one of three parameters: 90% </li></ul><ul><ul><li>Health Related Quality of Life Score </li></ul></ul><ul><ul><ul><li>Improved to 16.3 from 10.6 </li></ul></ul></ul><ul><ul><li>Vomiting Frequency Score </li></ul></ul><ul><ul><ul><li>Decreased to 1.9 [0.1] from 2.9 [0.1] </li></ul></ul></ul><ul><ul><li>Total GI Symptom Score </li></ul></ul><ul><ul><ul><li>Decreased to 10.9 [0.2] from 15.6 [0.3] </li></ul></ul></ul><ul><li>Gastric Emptying </li></ul><ul><ul><li>Two-hour retention fell from 55% to 42% </li></ul></ul><ul><ul><li>Four-hour retention fell from 26% to 17% </li></ul></ul>Results of Enterra™ Therapy 214 patients. 1992-2005. Univ. of Miss Med Ctr. Anand et al. Digestion 2007;75:83-89
    36. 36. Predictors of Poor Outcome <ul><li>Predominant symptoms: pain and bloating </li></ul><ul><li>Idiopathic gastroparesis </li></ul><ul><li>Loss of interstitial cells of Cahal on full thickness gastric biopsy </li></ul><ul><li>Electrogastrogram: tachygastric rhythm </li></ul>
    37. 37. Endoscopy-Placed, Trans-Nasal Electrodes: Evaluation of Response to Temporary Therapy
    38. 38. Gastroparesis <ul><li>Commoner than we think </li></ul><ul><li>Radio-labelled scintigraphy </li></ul><ul><li>Optimise diabetes treatment </li></ul><ul><li>Nutrition </li></ul><ul><li>Symptom-control </li></ul><ul><li>Enterra ™ </li></ul>
    39. 39. Controversies <ul><li>Quality of evidence: Weak </li></ul><ul><ul><li>Only one RCT – poor </li></ul></ul><ul><ul><li>Variable scoring systems </li></ul></ul><ul><ul><li>Attrition bias </li></ul></ul><ul><li>Confounded by concurrent pharmacotherapy </li></ul><ul><li>Relationship between delayed emptying and symptoms is unclear </li></ul><ul><li>Mechanism of action is unclear </li></ul>